Bleeding tendency in children with biliary atresia

Sixty-eight childrenwith biliary atresia (BA) were admitted to the Department of Pediatric Surgery, Kyushu University Faculty of Medicine and fukuoka Municipal Children's Hospital, from 1971 to 1986. In 11 (16.2%) there was a tendency toward bleeding associated with obstructive jaundice and breast feeding. In 4 of the 11 cases, vitamin K deficiency (VKD) was diagnosed by coagulation studies. The bleeding tendency improved after administrationn of vitamin K in all 4 cases; the other 7 were also suspected of having VKD. The usefulness of the Normotest [7] for the diagnosis of VKD and for mass screening of infantile hepatobiliary disorders, particularly BA, is discussed.     

Type I biliary atresia without extrahepatic biliary cyst

Currently, magnetic resonance cholangiography (MRC) is used for the differentiation of biliary atresia (BA) from other causes of infantile cholestasis. The authors present a case of type I BA without an extrahepatic biliary cyst in a 2-month-old girl. MRC clearly visualized the patency of the gallbladder, cystic duct, and hepatic ducts with disappearance of the common bile duct. Intraoperative cholangiography demonstrated a cloudy appearance of the intrahepatic bile ducts, confirming the diagnosis of type I BA. We believe that this is the first reported case of type I BA without an extrahepatic biliary cyst diagnosed by MRC.     

胆道闭锁肝内外胆系组织病理形态学分析

目的 通过胆道闭锁（BA）肝门纤维块、肝脏组织的病理及其超微结构观察，对肝门成纤维细胞分化程度进行评分，并与肝纤维化分级进行相关分析。方法 选取BA患儿作为研究对象，术中取肝门纤维块及肝脏组织标本；研究同期选取疑似BA经术中胆道造影除外BA，诊断为胆汁淤积综合征和先天性胆管扩张症患儿作为对照组，留取肝脏组织标本。在光镜和电镜下观察标本的病理改变，以及肝细胞、毛细胆管和肝门成纤维细胞的超微结构。采用SPSS 14.0软件，半定量比较BA与对照组肝脏纤维化的差异，检验肝门纤维块成纤维细胞活跃程度与肝纤维化分级的相关性。结果 2005年7月至2006年5月复旦大学附属儿科医院收治的21例BA Kasai根治术病例，手术平均年龄（66±20）d；对照组为5例胆汁淤积综合征和10例先天性胆管扩张症患儿。BA组肝组织病理改变主要是肝内门脉区胆管炎症及纤维化形成，肝纤维化程度明显高于同年龄胆汁淤积综合征和先天性胆管扩张症患儿；肝门纤维块毛细胆管增生，部分管腔闭锁、狭窄，腔内炎细胞浸润及部分淤胆，大量间质成分增生；电镜下肝门成纤维细胞活跃、肝脏毛细胆管上皮微绒毛缺失、肝细胞及肝血窦内电子致密物质增多及部分毛细胆管扩张；肝门成纤维细胞分化程度与肝组织纤维化程度相关（P=0.04）。结论 BA肝组织病理改变主要是肝内门脉区胆管炎症及严重纤维化形成；超微结构改变提示肝门部成纤维细胞活跃，其分化程度与肝纤维化程度相关。     

Bleeding disorder as the first symptom of biliary atresia.

Biliary atresia (BA) is occasionally diagnosed in infants whose first symptom is a bleeding disorder, such as intracranial bleeding, nasal bleeding or gastrointestinal bleeding. The authors describe 3 cases in which a bleeding disorder was the first symptom of BA. The presenting symptom was intracranial bleeding in a male on day 55 after birth, nasal bleeding in a female at 65 days, and gastrointestinal bleeding in a female at 25 days. Coagulation studies revealed a vitamin K deficiency in all patients. After the administration of vitamin K, the results of coagulation tests normalized and the bleeding tendency of the infants ceased. Subsequently, BA was suspected to be the cause of these bleeding disorders based on imaging findings. BA should therefore be considered in all infants with sudden onset of a tendency to bleed.     

Oesophageal atresia and biliary atresia: a rare association

Oesophageal atresia is known to be associated with cardiovascular, gastrointestinal, genitourinary and skeletal anomalies. Its association with biliary atresia is very rare and only a few cases have been reported in the literature. Although biliary atresia could be part of a multiple anomaly syndrome, its isolated occurrence is even rare. We present a case of oesophageal atresia associated with biliary atresia.     

A case of biliary atresia with cystic dilatation of the extrahepatic bile duct and polysplenia syndrome

A 79-day-old girl presented with jaundice and acholia. Laboratory findings disclosed elevated levels of bilirubin, transaminases, and gamma-glutamyl transferase. A chest X-ray film showed dextrocardia. A computed tomographic scan revealed a cystic mass at the porta hepatis, multiple spleens in the right side of the abdomen, and absence of the inferior vena cava. Under the diagnosis of biliary atresia (BA) (I-cyst) associated with polysplenia syndrome, a hepatic portojejunostomy was performed at 80 days of age. The postoperative course was uneventful, and the jaundice cleared. Although the occurrence of associated anomalies in BA is rare, polysplenia is most commonly seen, and its incidence is reported to be 2% to 10%. Patients with BA and polysplenia usually have a poor prognosis, however, this patient may have a good prognosis due to uneventful recovery from the jaundice. Accepted: 30 August 1999     

Bone density and 25-hydroxyvitamin D level in extrahepatic biliary atresia

Biliary atresia (BA) represents a common cholestatic affliction of the gastrointestinal tract affecting infants and children. The objective of the present study was to evaluate 42 patients (20 with and 22 without jaundice) diagnosed with extrahepatic BA for bone mineral content and serum 25-hydroxyvitamin D (HVD) levels. Physical examination and anthropometric nutritional assessment were performed. The investigation included liver function tests and serum calcium (Ca), phosphate (P), magnesium (Mg), and 25-HVD levels. Dual-energy X-ray absorptiometry was used to measure the bone mineral density (BMD) of the lumbar spine (L₁–L₄). Our results showed that 16 jaundiced␣patients (80%) and only 3 nonjaundiced patients (13.6%) showed osteoporosis (P< 0.05). All patients had normal serum Ca and P levels. Only 1 nonjaundiced patient had a low serum Mg level. Serum 25-HVD levels (mean ± SD) were 20.71 ± 8.24, 16.12 ± 4.3, and 9.18 ± 5.84 ng/ml, respectively, in subjects with normal bone density (n=7), osteopenia (n=3), and osteoporosis (n=11). Bone disease represents a well-known complication among long-term survivors of BA. To date, the pathogenesis has remained unexplained. Since, as demonstrated in the present study, jaundiced patients develop osteoporosis more frequently than nonjaundiced patients, hyperbilirubinemia may have an influence. Bone-mineral deficiency can be detected earlier by means of BMD measurement (non-invasive method) than by measuring serum Ca, P, and Mg levels in these patients. Accepted: 27 November 2000     

胆管闭锁与十二指肠乳头异位的关系探讨

目的 胆管闭锁的病因目前尚不清楚,本研究对胰胆的解剖进行造影研究.方法 对221 例胆管闭锁患儿中 47 例(21.3%)进行胆管造影,根据胆囊管和胆总管及十二指肠显影清晰影像进行研究,观察胆总管、胰管、胰胆合流共同管及其开口部位.以同期收治的 29 例非胆管闭锁性黄疸婴儿的胆管造影结果 为对照.结果 对照组29例中7例(24.1%)十二指肠乳头开口于十二指肠降段以远,而胆管闭锁组 47 例中 24 例(51.1%)十二指肠乳头开口于十二指肠降段以远,后者较前者明显增高(P<0.05).胆管闭锁组和对照组合并胰胆合流异常的发生率分别为95.7%(45/47)和82.8%(24/29),二者差异无显著性意义(P>0.122).胆管闭锁患儿胰胆合流共同管的平均长度指数为0.418±0.152,比对照组(0.236±0.122)明显延长,P<0.05.胆管闭锁组胆总管的平均直径指数为0.078±0.043,对照组为0.199±0.086,前者较后者明显细小,P<0.05,而共同管和胰管的直径差异不显著(P>0.05).结论 十二指肠乳头远端开口异位和胰胆合流共同管延长是胆管闭锁影像学改变特点,提示此畸形的病因与胚胎早期肝憩室发育异常有关.     

十二指肠内胆红素光吸收值监测在胆道闭锁诊断中的应用研究

目的本研究对〈4个月阻塞性黄疸婴儿十二指肠内的胆红素进行光吸收值动态监测，评价光吸收值在胆道闭锁诊断中的意义。方法研究对象分为胆道闭锁患儿（biliary atresia，BA）17例（男11例，女6例；年龄2～16周，平均5．7周）及婴儿肝炎综合征患儿（infantile hepatitis syndrome，IHS）20例（男14例，女6例；年龄3～7周，平均5周）。37例患儿接受了Bilitec十二指肠内胆红素光吸收值的监测，观察原始光吸收值曲线图，分析、比较最高光吸收值、光吸收值≥0．14U及≥0．25U的时间百分比。结果胆道闭锁组的光吸收值明显低于婴儿肝炎综合征组。结论十二指肠内胆红素光吸收值监测可为鉴别BA与IHS提供客观依据。     

影响胆道闭锁早期诊治的原因分析

目的：分析影响胆道闭锁早期诊断和治疗的因素并探讨解决对策。方法：回顾性总结与分析70例胆道闭锁患儿就诊年龄与临床表现、主诊医生和家长对本病的认识、影像学检查结果等方面对早期诊断的影响，探讨延误诊治的各种原因。结果：影像学检查中，肝胆核素检查27例，6例误诊。B超检查在未掌握观察肝门纤维块前，23例中仅有14例诊断正确，而在掌握该方法后，检查38例，35例诊断正确。结论：先天性胆道闭锁延误诊治的原因有：临床表现不典型、观察病情不细致、主诊医生对本病的认识不足、影像学检查的误诊等。因此建议：仔细体检,医生亲自观察大便颜色；B超检查内容包括观察肝门纤维块和胆囊进食前后的变化。肝胆核素检查， 应防止放射物污染，减少同位素在体内的分解水化。     

Extrahepatic biliary atresia associated with trisomy 18

A case of extrahepatic biliary atresia (EBA) associated with trisomy 18 is presented. A 1-month-old boy was suspected to have Alagille syndrome with obstructive jaundice, a systolic heart murmur, growth retardation, and a small, pointed chin. However, surgery and chromosomal analysis revealed EBA associated with trisomy 18. Chromosomal examination must be performed in patients with jaundice and congenital anomalies. It is possible that EBA in trisomy 18 syndrome is due to a chromosomal disorder. Accepted: 20 April 1998     

Computerized three-dimensional study of a rotavirus model of biliary atresia: comparison with human biliary atresia

Biliary atresia is a panbiliary disease causing obstructive jaundice in neonates and infants. The clinical spectrum can be broadly categorized into the fetal and perinatal types. A consistent animal model that accurately mimics the whole clinical spectrum of biliary atresia is not yet available. However, rotavirus infection of neonatal mice has been shown to produce atresia in the biliary system. This study investigates the three-dimensional computerized morphology of the murine neonatal model comparing with age-matched control mice. Newborn Balb/c mice were injected intraperitoneally with rhesus rotavirus within 24–48 h after birth. Control mice received 0.9% NaCl. Pups with symptoms of cholestasis were sacrificed from the 5th to the 15th postinjection day, as were age-matched controls. Their hepatobiliary tissues were prepared for three-dimensional computerized image reconstruction. Rotavirus infection caused obliteration of the intrahepatic bile ducts and single to multiple atresias in the extrahepatic bile duct. At 15 days postinjection, intrahepatic ductal proliferation appeared, and the three-dimensional appearances of the intrahepatic biliary structures were similar to the human disease. Cystic duct and gallbladder dilatation was frequently seen in this model, and this feature distinguishes it from the human disease in which the gallbladder is almost always atretic. This rotavirus murine model demonstrates many of the features of human perinatal biliary atresia, and can be used as an investigative tool to further study the pathogenesis of biliary atresia.     

胆道闭锁术中胆汁流量及胆汁成分的观察分析

目的 探讨胆道闭锁术中胆汁流量及成分变化与预后的关系.方法 本组对27例BA患儿行Kasai手术时,采用5 ml气体采样管收集和测量从肝门流出的胆汁.以17例胆总管囊肿患儿术中收集的胆汁作为对照组,其中测胆汁流量者7例.采用全自动生化仪检测胆汁中磷脂、总蛋白(TP)、胆汁酸(TBA)、总胆红素(TBIL)、直接胆红素(DBIL)、总胆固醇(TC)、谷草转氨酶(AST)、谷丙转氨酶(ALT)、谷氨酰胺转肽酶(GGT)、碱性磷酸酶(ALP)的浓度.术后随访1～6个月,随访内容有黄疸消退时间、术后血生化、术后胆管炎发生情况.结果 BA组胆汁流量显著低于对照组(P<0.05).手术日龄>60 d的BA患儿及术前血ALT>150 U/L的BA患儿术中胆汁流量均显著低于对照组(P<0.05).术中胆汁流量≥0.19 ml/min的BA患儿术后3个月退黄率显著高于术中胆汁流量<0.19 ml/min的BA患儿(P<0.05).BA组的胆汁磷脂、TBA及DBIL浓度均显著低于对照组(P<0.05);BA组的胆汁ALT浓度显著高于对照组(P<0.01).术后3个月黄疸消除者的胆汁AST及TC浓度均显著低于未消除者(P<0.05).结论 BA术中胆汁流量与预后有明显的关系,患儿术中胆汁流量越好,术后的预后越好,提示术中胆汁流量可以更早地预测患儿的远期效果.BA胆汁成分的变化说明BA患儿的肝功能较差,胆汁中磷脂、TBA和DBIL浓度较低可能是肝脏分泌功能较差的表现.胆汁中的AST和TC浓度与预后有关,胆汁AST和TC浓度较低的BA患儿术后预后较好,可能是由于肝功能较好和胆汁粘度较低利于引流所致.     

Long-term survival after Kasai's operation for biliary atresia

Long-term survival of biliary atresia patients after Kasai hepaticoportoenterostomy is being increasingly reported. Prognostic factors indicative of a favorable long-term outcome consist of: (1) early age at operation; (2) bilirubin excretion of at least 6 mg daily 1 month after operation; (3) favorable hepatic histology at the time of operation; and (4) low incidence of postoperative cholangitis. Jaundice-free long-term survival is now attained in from one-fourth to one-third of patients undergoing Kasai hepaticoportoenterostomy by experienced surgeons in the Western hemisphere. In many long-term survivors there is normalization of liver function, improvement in hepatic histology, and resolution of the complications of portal hypertension. Most patients in this category have made a normal adjustment to their disease and lead active adolescent and adult lives. Offprint requests to: B. A. Stewart     

Use of appendix in biliary atresia

Antiperistaltic appendiceal conduit based on its vascular pedicle was used as hepaticoporto-appendico-jejunostomy (HAJ) in 9 infants with advanced stage of biliary atresia. Operative procedure was simple and less time consuming. The postoperative cholangitis was conspicuously absent, possibly due to the role played by the presence of lymphoid follicles in the wall of the appendix. Our early experience with this technique shows that antiperistaltic appendiceal conduit works quite satisfactorily. The procedure has been successfully utilised to reduce the problems contributing post-operative morbidity and mortality in cases with the advanced disease. The HAJ procedure provides a conduit for bilioenteric drainage, that closely resembles to normal anatomy.     

MicroRNA在胆道闭锁中的研究进展

小分子核糖核酸(microRNA,miRNA,miR)是一类约22个核苷酸的单链非编码RNA,在转录后水平调节基因的表达.miRNA广泛存在于人体各个组织器官中,在细胞增殖、分化、凋亡、胚胎发育、信号传导、肿瘤发生及代谢等过程中发挥着重要作用.近年来研究表明,某些miR-NA表达的改变在胆道闭锁的发生发展中起着重要作用,在该过程中体现出极其复杂的调控机制,同时miRNA的研究也为胆道闭锁的早期诊断和治疗带来了新的希望和思路.本文就miRNA在胆道闭锁中的研究进展做一综述.     

An ovarian dysgerminoma in a girl with biliary atresia

We present a case of an ovarian dysgerminoma in an 11-year-old girl who had had a hepatic porto-jejunostomy for biliary atresia (BA) when she was 1 month old. Although the tumor was successfully treated with surgery followed by radiotherapy, she died of hepatic failure 12 months after operation. The incidence of malignant disease in patients with BA is extremely low, and the etiologic correlation between the two diseases still remains unclear.     

胆道闭锁患儿5种嗜肝DNA病毒感染状况检测报告

目的 检测几种常见嗜肝DNA病毒在胆道闭锁患儿肝脏组织中的感染率,探讨其与胆道闭锁发生的关系.方法 用荧光定量PCR(FQ-PCR)检测随机选取的85例胆道闭锁和10例对照组患儿肝脏组织中的5种嗜肝DNA病毒,包括人巨细胞病毒(HCMV)、腺病毒(ADV)、EB病毒(EBV)、单纯疱疹病毒(HSV)和乙肝病毒(HBV),同时进行石蜡切片的病理染色和巨细胞病毒晚期蛋白PP65免疫组化方法检测.结果 在85例胆道闭锁患儿肝脏组织中,嗜肝DNA病毒阳性56例(65.9%),其中HCMV阳性51例(60.0%),ADV阳性5例(5.9%),EBV阳性3例(3.5%),HSV和HBV阳性0例(0%),对照组10例中均未检测到以上病毒的存在.免疫组织化学结果显示:HCMV多集中于肝脏组织中的肝细胞、血管内皮细胞、炎症浸润细胞当中,胆管上皮细胞呈强阳性反应.结论 胆道闭锁与嗜肝DNA病毒感染之间存在相关性,其中以人巨细胞病毒感染关系最为密切.     

胆道闭锁Kasai手术效果影响因素的研究进展

胆道闭锁(biliary atresia,BA)是肝内外胆管进行性纤维化引起肝内外胆管硬化和闭锁的一种常见疾病,Kasai手术(肝门空肠吻合术)改善了患儿预后.手术时肝脏的病理状态,包括肝脏纤维化程度、胆管板畸形、肝门部纤维斑块、胆道闭锁类型都对Kasai术后的效果有影响.单纯用年龄评价手术预后有欠妥当.建立胆道闭锁治疗中心以提高外科医师实施Kasai手术的经验有助于改善手术预后,而胆道闭锁脾脏畸形综合征、早产儿、CMV感染对预后有不利影响.激素、熊去氧胆酸及抗生素的预防性使用其有效性目前尚有争议.     

胆道闭锁血清蛋白质标记物的检测

目的 寻找特异性诊断胆道闭锁的血清蛋白标记物.方法 应用表面增强激光解吸电离飞行时间质谱(SELDI-TOF-MS)技术检测28例血清标本(胆道闭锁7例,先天性胆总管囊肿7例,婴肝综合征3例,正常对照11例)的蛋白质质谱表达,结合生物信息学方法(SVM)分析数据.结果 筛选出m/z位于3403、2108、2111、2131、2823的5个蛋白质标记物区分肝胆疾病和正常对照小儿的血清蛋白指纹图谱模型,敏感性94.1%,特异性81.8%;筛选出m/z位于3403蛋白质标记物区分胆道闭锁和正常对照小儿的血清蛋白指纹图谱模型,敏感性100%,特异性100%;筛选出m/z位于3403、4796的2个蛋白质标记物区分胆道闭锁和其他肝胆疾病的血清蛋白指纹图谱模型,敏感性71.4%,特异性80.0%.结论 应用SELDI-TOF-MS结合SVM构建的胆道闭锁血清蛋白指纹图谱模型为胆道闭锁的早期诊断方法开拓了新方向,值得进一步研究.